F. Honoraria; Genentech. G. Consultant; Genentech, Bristol-Myers. Squibb. J.R. Brahmer: E. Research Grant; Bristol-Myers Squibb. G. Consultant; Bristol-Myers ...
Volume 90 Number 5S Supplement 2014 duration of response [mDOR] not reached [NR]; range 6.1+, 49.1+); 6/8 responders achieved a response by first scan (wk 10); 6 pts had ongoing responses. Overall, 16 pts (33%) had a best overall response of stable disease. Three pts exhibited unconventional responses. At the N1 + I3 mg/ kg dose, ORR, median progression-free survival (mPFS) and 24-week PFS rate were 11% (1/9), 8.9 wks and 25% for sq pts, and 13% (2/15), 32.9 wks and 51% for non-sq pts, respectively; mDOR was NR (all responses ongoing). At N3 + I1 mg/kg, ORR, mPFS and 24-week PFS rate were 33% (3/9), 20.6 wks and 44% for sq pts, and 13% (2/16), 9.9 wks and 20% for non-sq pts, respectively; mDOR was 21.0 wks (range 12.1, 21.0 wks) in sq pts and NR in non-sq pts (range 32.1+, 49.1+) with 1 sq and 2 non-sq responses ongoing. At the time of analysis, tumor samples from 38 pts had been tested for PD-L1 (16 PD-L1+, 22 PD-L1-); ORs were observed in both PD-L1+ (19%) and PD-L1- (14%) pts. Conclusions: These interim results suggest treatment with nivolumab + ipilimumab is feasible in pts with advanced NSCLC, with early, durable antitumor activity in pts with both PD-L1+ and PD-L1- tumors. Safety and clinical activity will also be presented for a N1 + I1 mg/kg cohort. Author Disclosure: S.J. Antonia: E. Research Grant; MedImmune. F. Honoraria; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb. S. Gettinger: G. Consultant; Bristol-Myers Squibb. K. Advisory Board; Bristol-Myers Squibb. J. Goldman: E. Research Grant; Bristol-Myers Squibb, Genentech. L.Q. Chow: E. Research Grant; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. R. Juergens: E. Research Grant; BristolMyers Squibb. H. Borghaei: E. Research Grant; Pfizer, Arisaph, Millenium. F. Honoraria; Genentech. G. Consultant; Genentech, Bristol-Myers Squibb. J.R. Brahmer: E. Research Grant; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. Y. Shen: A. Employee; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. C. Harbison: A. Employee; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. A.C. Chen: A. Employee; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. N.E. Ready: E. Research Grant; BristolMyers Squibb. K. Advisory Board; Bristol-Myers Squibb. N.A. Rizvi: F. Honoraria; Bristol-Myers Squibb, Genentech/Roche, Medimmune. G. Consultant; Bristol-Myers Squibb.
169 Efficacy and Safety of Ceritinib in Patients With Advanced Anaplastic Lymphoma Kinase (ALK)-Rearranged (ALK+) Non-Small Cell Lung Cancer (NSCLC): An Update of ASCEND-1 Metastatic Non-Small Cell Lung Cancer D. Kim,1 R. Mehra,2 D.S.W. Tan,3 E. Felip,4 L.Q.M. Chow,5 D.R. Camidge,6 J. Vansteenkiste,7 S. Sharma,8 T. De Pas,9 G.J. Riely,10 B.J. Solomon,11 J. Wolf,12 M. Thomas,13 M. Schuler,14 G. Liu,15 A. Santoro,16 M. Geraldes,17 A.L. Boral,18 A. Yovine,19 and A.T. Shaw20; 1 Seoul National University Hospital, Seoul, Korea, Republic of, 2Fox Chase Cancer Center, Philadelphia, PA, 3National Cancer Centre Singapore, Singapore, Singapore, 4Vall d’Hebron University, Barcelona, Spain, 5University of Washington, Seattle, WA, 6University of Colorado, Denver, CO, 7University Hospital KU Leuven, Leuven, Belgium, 8 Huntsman Cancer Institute, Salt Lake City, UT, 9Instituto Europeo di Oncologia, Milan, Italy, 10Memorial Sloan Kettering Cancer Center, New York, NY, 11Peter MacCallum Cancer Centre, East Melbourne, Australia, 12 University Hospital Cologne, Cologne, Germany, 13Thoraxklinik, University of Heidelberg, Heidelberg, Germany, 14University Hospital Essen, Essen, Germany, 15Princess Margaret Cancer Centre, Toronto, ON, Canada, 16IRCCS Institute Clinico Humanitas, Milan, Italy, 17Novartis Pharmaceuticals Corporation, East Hanover, NJ, 18Novartis Institutes for BioMedical Research, Cambridge, MA, 19Novartis Pharma AG, Basel, Switzerland, 20Massachusetts General Hospital, Boston, MA Purpose/Objective(s): ALK+ tumors (2-7% of NSCLC) are sensitive to ALK tyrosine kinase inhibitors such as crizotinib (CRZ), although resistance invariably develops. Ceritinib (LDK378), a novel ALK inhibitor (ALKi), is more potent than CRZ in vitro and is effective in CRZ-resistant disease. Updated data from the ASCEND-1 study (NCT01283516) are
Poster Presentations
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presented with a focus on patients receiving ceritinib at the recommended dose of 750 mg/day and with a longer follow-up compared with prior presentation. Materials/Methods: Investigator assessment of efficacy is presented for patients with ALK+ NSCLC who received at least 1 dose of ceritinib at 750 mg/day prior to 31 Oct 2013. Results with additional follow-up will be presented. Results: The 246 patients with ALK+ NSCLC receiving ceritinib 750 mg/ day had a median duration of follow up of 7 months. Of these, 230 (93%) had received prior antineoplastic therapy, 166 (67%) with 2 prior regimens and 163 (66%) had received a prior ALKi (CRZ in all patients). Among these ALKi-pretreated patients, 91% had progressive disease and 78% had received ALKi as their last prior therapy. Overall response rate was 58.5% (95% CI; 52.1, 64.8) for all patients, 54.6% (46.6, 62.4) for ALKi-pretreated patients and 66.3% (55.1, 76.3) for ALKi-naı¨ve patients. Median time to first response was 6.1 weeks for all cohorts; median DOR was 9.7 (95% CI; 7.0, 11.4) months for all patients and 7.4 (5.4, 10.1) months in ALKi-pretreated patients and was not yet estimable in the ALKnaı¨ve cohort. Median PFS was 8.2 months (95% CI; 6.7, 10.1) and 6.9 (5.4, 8.4) months for all patients and the ALKi-pretreated cohort, respectively, and was not yet estimable for the cohort of ALK-naı¨ve patients. Discontinuation of treatment due to an adverse event (AE) occurred in 24 (10%) patients with NSCLC; 17 (10%) ALKi-pretreated patients and 7 (8%) ALKi-naı¨ve patients. Among all 255 patients receiving ceritinib 750 mg/ day in the safety population, 99 (39%) required 1 ceritinib dose reduction and 51 (20%) required 1 dose reductions. The most common AEs of any grade (>50%) were diarrhea (86%), nausea (80%), vomiting (60%), abdominal pain (54%) and fatigue (52%). Most common lab abnormalities (>50%) were decreased hemoglobin (84%), increased ALT (80%), increased AST (75%), increased creatinine (58%). Most common grade 3/ 4 lab abnormalities (>10%): increased ALT (27%) increased AST (13%), increased glucose (13%). One treatment-related death (interstitial lung disease) was reported. Conclusions: Ceritinib 750 mg/day shows potent antitumor activity in ALK+ NSCLC patients regardless of prior ALKi treatment status. Discontinuation due to toxicity was uncommon. Author Disclosure: D. Kim: F. Honoraria; Pfizer, Lilly. G. Consultant; Novartis, Pfizer, Lilly. R. Mehra: A. Employee; Spouse is employee of GlaxoSmithKline. G. Consultant; Bristol Meyers Squibb, Novartis. I. Travel Expenses; Pfizer, Bristol Meyers Squibb, Novartis. K. Advisory Board; Novartis, Bristol Meyers Squibb. D.S.W. Tan: None. E. Felip: K. Advisory Board; Boehringer Ingelheim, Novartis, Roche, Bristol Meyers Squibb, Lilly. L.Q.M. Chow: A. Employee; University of Washington. E. Research Grant; Novartis LDK Study. I. Travel Expenses; Novartis Advisory Board. K. Advisory Board; Novartis. L. Funding Other; Research support for three Novartis sponsored clinical trials (funds directly to University of Washington). D.R. Camidge: F. Honoraria; Ariad, Boehringer Ingelheim, Synta, Array Biopharma, Pfizer. K. Advisory Board; Servier, Eli Lilly, Genentech/Roche, Astex, Ariad, ImmunoGen, Clarient, Excelixis, IndiPharm, Astellas, Boehringer Ingelheim, Chugai, Clovis, Array Biopharma, AstraZeneca, Aveo, Novartis, Synta. L. Funding Other; Ariad. J. Vansteenkiste: H. Speakers Bureau; Novartis. S. Sharma: E. Research Grant; Novartis. G. Consultant; Novartis. M. Stock; Salarius Pharmaceuticals, Beta Cat Pharmaceuticals, ConverGene. S. Leadership; TheraTarget, UBL Therapeutics IDMC. T. De Pas: None. G.J. Riely: K. Advisory Board; Chugai, Ariad, Daiichi, Tragara, Foundation Medicine, Boehringer-Ingelheim, Novartis. L. Funding Other; Pfizer, Bristol-Myers, Chugai, GSK, Novartis, Infinity. B.J. Solomon: F. Honoraria; Novartis, Pfizer, AstraZeneca, Roche, Clovis Oncology. K. Advisory Board; Novartis, Pfizer, AstraZeneca, Roche, Clovis Oncology. J. Wolf: E. Research Grant; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. F. Honoraria; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. G. Consultant; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. H. Speakers Bureau; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. I. Travel Expenses; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. K. Advisory Board; AstraZeneca, Novartis, Roche, Pfizer, Boehringer-Ingelheim, BMS, Clovis. L. Funding
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International Journal of Radiation Oncology Biology Physics
Other; Novartis, Roche, Boehringer-Ingelheim. M. Thomas: F. Honoraria; Lilly, Bristol Meyers Squibb, Roche. G. Consultant; Lilly, Bristol Meyers Squibb, Roche, Novartis. M. Schuler: E. Research Grant; Boehringer Ingelheim, Novartis. F. Honoraria; Boehringer Ingelheim, Celgene, GlaxoSmithKline, Lilly, Novartis, Pfizer. G. Consultant; AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer. G. Liu: G. Consultant; Astra Zeneca, Pfizer, Novartis. A. Santoro: None. M. Geraldes: A. Employee; Novartis Pharmaceuticals. M. Stock; Novartis Pharmaceuticals. A.L. Boral: A. Employee; Novartis Pharmaceuticals. A. Yovine: A. Employee; Novartis Pharma AG. A.T. Shaw: G. Consultant; Ignyta. K. Advisory Board; Novartis, Pfizer, Ariad, Chugai, Genentech.
unresolved grade 3+ pneumonitis (2 deaths were early in the trial; the third occurred after the March 2013 safety analysis). Conclusions: In heavily pretreated pts with advanced NSCLC, nivolumab demonstrated durable clinical activity, 1- and 2-yr OS rates of 42% and 24%, and a manageable safety profile. Algorithms are in place to assist with identification and management of pneumonitis. Additional follow-up for survival and response duration will be presented. These longer term results support the ongoing evaluation of nivolumab in NSCLC pts. Author Disclosure: S.N. Gettinger: G. Consultant; Bristol-Myers Squibb. K. Advisory Board; Bristol-Myers Squibb. L. Horn: E. Research Grant; Astellas. G. Consultant; Bayer. H. Speakers Bureau; Boehringer Ingelheim. I. Travel Expenses; Boehringer Ingelheim. K. Advisory Board; Bristol Myers Squibb, Helix BioPharma, Xcovery, Clovis, PUMA. L. Gandhi: None. D.R. Spigel: G. Consultant; Bristol-Myers Squibb. S.J. Antonia: E. Research Grant; Medimmune. F. Honoraria; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb. N.A. Rizvi: F. Honoraria; Bristol-Myers Squibb, Genentech/Roche, Medimmune. G. Consultant; Bristol-Myers Squibb. J.D. Powderly: A. Employee; Biologics Human Application Lab. E. Research Grant; Bristol-Myers Squibb, Genentech, Amplimmune, Merck. F. Honoraria; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb, Genentech, Amplimmune, Merck. H. Speakers Bureau; Bristol-Myers Squibb. K. Advisory Board; Bristol-Myers Squibb. R.S. Heist: E. Research Grant; Genentech, Novartis, GlaxoSmithKline, Pfizer, Debiopharm. R.D. Carvajal: G. Consultant; Aura Biosciences. D.M. Jackman: F. Honoraria; Roche. G. Consultant; Genentech, Foundation Medicine, Cowen Group. L.V. Sequist: G. Consultant; Clovis, Boehringer Ingelheim, AstraZeneca, Merrimack, Novartis, Taiho. D.C. Smith: E. Research Grant; Bristol-Myers Squibb. P.D. Leming: None. S.L. Topalian: E. Research Grant; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb, Jounce Therapeutics, Sanofi, Amplimmune. N. Stock Options; Compugen, Amplimmune, NexImmune, Jounce Therapeutics. P. Royalty; Bristol-Myers Squibb, Amplimmune. F. Hodi: G. Consultant; Bristol-Myers Squibb. M. Sznol: G. Consultant; Bristol-Myers Squibb, Nektar, Amgen, Genentech, Symphogen, Anaeropharma, MedImmune. C.T. Harbison: A. Employee; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. G.D. Kollia: A. Employee; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb. J.R. Brahmer: E. Research Grant; Bristol-Myers Squibb. G. Consultant; Bristol-Myers Squibb. M. Stock; Bristol-Myers Squibb.
170 Long-term Survival, Clinical Activity, and Safety of Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) in Patients (Pts) With Advanced Non-Small Cell Lung Cancer (NSCLC) Metastatic Non-Small Cell Lung Cancer S.N. Gettinger,1 L. Horn,2 L. Gandhi,3 D.R. Spigel,4 S.J. Antonia,5 N.A. Rizvi,6 J.D. Powderly,7 R.S. Heist,8 R.D. Carvajal,6 D.M. Jackman,3 L.V. Sequist,8 D.C. Smith,9 P.D. Leming,10 S.L. Topalian,11 F. Hodi,3 M. Sznol,1 C.T. Harbison,12 G.D. Kollia,12 and J.R. Brahmer11; 1Yale Cancer Center, New Haven, CT, 2Vanderbilt University Medical Center, Nashville, TN, 3Dana-Farber Cancer Institute, Boston, MA, 4Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, 5H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 6Memorial Sloan Kettering Cancer Center, New York, NY, 7Carolina BioOncology Institute, Huntersville, NC, 8Massachusetts General Hospital Cancer Center, Boston, MA, 9University of Michigan, Ann Arbor, MI, 10The Christ Hospital Cancer Center, Cincinnati, OH, 11The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 12 Bristol-Myers Squibb, Princeton, NJ Purpose/Objective(s): Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, demonstrated durable clinical activity and a manageable safety profile in a large phase 1b trial of treatment-refractory pts with advanced solid tumors, including melanoma, kidney cancer and NSCLC. Here we report long-term safety, efficacy, and overall survival (OS) by dose and histology in the NSCLC cohort. Materials/Methods: Previously treated pts with advanced NSCLC (nZ129) received nivolumab 1, 3, or 10 mg/kg IV Q2W for a maximum of 96 weeks in the outpatient setting. Tumor assessment was based on RECIST 1.0. Objective response (OR) was evaluated by key pt characteristics. Tumor cell PD-1 ligand 1 (PD-L1) expression in archived pretreatment tumor samples (nZ68) was measured using a Dako immunohistochemistry assay (PD-L1+ defined as 5% of tumor cells with cell surface staining). Results: Of the 129 pts treated (74 non-squamous [sq], 54 sq, 1 unknown), 54% had received 3 prior therapies. Across doses, OR rate was 17% (22/129), with a median duration of response of 74 wks (range 6.1+, 133.9+) and ongoing responses in 45% (10/22). Response was observed at first tumor assessment (wk 8) in 50% of responders and 10% of pts had stable disease for 24 wks. ORs were observed in pts with PD-L1+ and PD-L1- tumors (15% and 14%, respectively). Clinical activity was observed across all pt subgroups regardless of histology, number of prior therapies, age, or EGFR or KRAS mutation status. Median OS was 9.9 months (14.9 months at 3 mg/kg dose). One-yr and 2-yr OS rates were 42% and 24%, respectively; 1-yr and 2-yr OS rates for 1, 3, and 10 mg/kg doses were 32% and 12%, 56% and 45%, and 40% and 19%, respectively. OS rates were similar across histologies (1-yr, 40%-43%; 2-yr, 23%24%). In pts with PD-L1+ and PD-L1- tumors, median OS was 7.8 (95% CI 5.6, 21.7) and 10.5 (5.2, 21.2) months, respectively; median PFS was 3.6 (1.8, 7.5) and 1.8 (1.7, 2.3) months, respectively. Any grade treatment-related select adverse events (AEs) occurred in 41% of pts (5% grade 3-4). Grade 3-4 related AEs were reported in 14% (most common: fatigue, 3%). Three treatment-related deaths occurred, all associated with
171 Safety and Response With Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) Plus Erlotinib in Patients (Pts) With Epidermal Growth Factor Receptor Mutant (EGFR MT) Advanced Non-Small Cell Lung Cancer (NSCLC) Metastatic Non-Small Cell Lung Cancer S. Gettinger,1 L.Q. Chow,2 H. Borghaei,3 Y. Shen,4 C. Harbison,4 A.C. Chen,4 and N.A. Rizvi5; 1Yale Cancer Center, New Haven, CT, 2 University of Washington, Seattle, WA, 3Fox Chase Cancer Center, Philadelphia, PA, 4Bristol-Myers Squibb, Princeton, NJ, 5Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Preclinical studies demonstrate EGFR signaling in EGFR MT NSCLC leads to upregulation of tumor programmed death-1 (PD-1) ligand 1 and suppression of antitumor immunity. Treatment with an anti-PD-1 antibody in an EGFR MT murine NSCLC model relieved immune inhibition, reduced tumor growth, and promoted tumor cell apoptosis. Nivolumab is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody that has shown encouraging safety and clinical activity in pts with advanced NSCLC. The EGFR tyrosine kinase inhibitor (TKI) erlotinib is FDA-approved for the first-line treatment of EGFR MT NSCLC, yielding a median progression-free survival (PFS) of 10.4 months. We report interim results from a phase 1 study evaluating the safety and activity of nivolumab in combination with erlotinib in an EGFR MT, chemotherapy-naı¨ve, advanced NSCLC pt cohort. Materials/Methods: Chemotherapy-naı¨ve pts (NZ21) with stage IIIB/IV EGFR MT NSCLC (EGFR TKI naı¨ve or with progression after prior
